The effect of multiple single cannulation technique on complications of arteriovenous fistulae: A meta-analysis

Objective: To evaluate the effect of multiple single cannulation technique on the complications of arteriovenous fistula. Methods: A comprehensive literature search was conducted to investigate the impact of multiple single cannulation technique on the complications of arteriovenous fistula. The search was performed in both Chinese and English databases including Wanfang Medicine, China National Knowledge Infrastructure, Vip, Pubmed, Embase, and The Cochrane Library, with a search period up to December 20, 2023. Following literature screening and data extraction, the quality of the included studies was assessed using the Cochrane Bias Assessment Tool for Randomized Controlled Trials. Statistical analysis was performed using Review Manager version 5.3. Results: Thirteen papers, totaling 1299 patients, were included in the analysis. The experimental group consisted of 646 patients, while the control group had 595 patients. The meta-analysis revealed that the multiple single cannulation technique was more effective than rope ladder cannulation and buttonhole cannulation in reducing the incidence of angiomas (odds ratio [OR] = 0.19; 95% confidence interval [CI] = 0.10–0.35), stenosis (OR = 0.22; 95% CI 0.13–0.39), thrombosis (OR = 0.17; 95% CI = 0.07–0.39), and blood seepage (OR = 0.13; 95% CI = 0.08–0.21) of arteriovenous fistulas (P < .05). Additionally, it was found to increase the success rate of nurses’ single cannulation (OR = 4.20; 95% CI = 1.78–9.95) of arteriovenous fistulas (P < .05). Conclusion: Multiple single cannulation technique could effectively reduce the incidence of complications of arteriovenous fistula, improve the success rate of cannulation, prolong the life span of arteriovenous fistula, and prolong the survival cycle of hemodialysis patients.


Introduction
In recent years, there had been a gradual increase in the incidence of chronic kidney disease (CKD), which had a significant impact on the physical and mental health of the population.Epidemiological data indicate that the global prevalence of CKD was 13.4%, with the number of patients receiving renal replacement therapy ranging from 49.02 million to 70.83 million.In China, the prevalence of CKD among the population was10.8%,affecting approximately 120 million individuals. [1]he 3 main treatment options for end-stage CKD were kidney transplant, hemodialysis, and peritoneal dialysis.However, due to factors such as the scarcity of kidney donors, the high cost of transplantation, the risk of infection associated with peritoneal dialysis, and the challenges in managing peritoneal dialysis patients, hemodialysis had become increasingly prevalent in clinical practice.4] According to the data from China's hemodialysis case registration system, the number of hemodialysis patients in China reached 633,000 by the end of 2019. [5]Hemodialysis access options mainly included arteriovenous fistula (AVF) and dialysis catheter with polyester.Approximately 77.12% to 88.20% of hemodialysis patients in China used arteriovenous fistula for dialysis. [4,6]The Chinese hemodialysis vascular access consensus recommended that each dialysis center should use dialysis catheters for ≤10% of their patients, while the use of arteriovenous fistulas should be at least 80%. [7]emodialysis patients typically underwent dialysis 2 to 3 times per week, which required cannulation of the arteriovenous fistula around 280 times per year.However, this frequent cannulation could have negative effects on the patient's arteriovenous fistula.The most commonly used cannulation methods were rope ladder cannulation, buttonhole cannulation, and area puncture.Rope ladder cannulation required higher vascular conditions, with a minimum length of 6 cm and could cause complications such as hemangioma and arteriovenous fistula angiomatous dilatation, which in turn affect the patient's cardiac function.Buttonhole cannulation also had higher implementation requirements, as it required the same nurse to use the same angle and depth for consecutive cannulations until a complete subcutaneous tunnel was established.However, buttonhole cannulation was prone to fistula infections, which could lead to bacterial toxemia and, in severe cases, patient death.It was important to note that guidelines and expert consensus did not recommend the use of area puncture. [7,8]n recent years, a new cannulation method called multiple single cannulation technique has been proposed. [9]Domestic and foreign research on multiple single cannulation technology was relatively limited.Portuguese scholars had demonstrated that this method could effectively reduce complications associated with arteriovenous fistula, such as hematoma, angioma, and stenosis. [10,11]These complications could negatively impact dialysis adequacy and the lifespan of the arteriovenous fistula.[14][15][16] Therefore, this paper aimed to compare the effects of multiple single cannulation techniques on arteriovenous fistula through a Meta-analysis using evidence-based medicine.The findings of this study would provide a basis for selecting the best cannulation method for nursing practice.The methodology and results of this study were presented below.

Literature screening and data extraction
Literature was managed using Endnote X7, and 2 independent researchers (Luo Yiqi and Wen Zhuping) screened the literature and extracted data according to the literature inclusion and exclusion criteria for this study, with a third researcher (Wang Xia) exercising judgment when disagreements were encountered.The extracted data were cross-checked by 2 people and entered into Excel.The extracted data included the following: article title, author name, publication time, sample size of each group, study type, follow-up time, age, gender, dialysis age, follow-up time, and outcome indicators.

Evaluation of the quality of literature
Two authors independently evaluated the quality of the included studies using the Cochrane Risk of Bias 2 tool for randomised controlled trials. [17]The tool involves assessing 7 domains: randomization process (selection bias), concealment of the allocation sequence (selection bias), blinding of participants and health professionals (performance bias), blinding of outcome assessment (detection bias), missing outcome data (attrition bias), selective reporting of results (reporting bias), and other potential sources of bias.Assessment decisions were categorized as "low risk of bias," "high risk of bias," or "some concerns" low risk, the quality of the literature was graded A. When some dimensions were evaluated as low risk and there was no high risk, the quality of the literature was graded B. When 1 dimension was evaluated as high risk, the quality of the literature was graded C.

Statistical methods
Meta-analysis of the literature was performed using Review Manager 5.3 statistical software.The heterogeneity of the literature was tested using the chi-square test, if P > .1 and I 2 < 50%, indicating that there was no significant heterogeneity in the statistical results, a fixed-effects model was selected for analysis.If P < .1 and I 2 > 50%, indicating that there was significant heterogeneity in the statistical results, the causes of heterogeneity were first analyzed, if there was no clinical heterogeneity, a randomeffects model was selected for analysis; if clinical heterogeneity existed, a subgroup analysis was performed according to factors such as the type of complications.If there was no clinical heterogeneity, a random-effects model was chosen for analysis.Sensitivity analysis was used for publication to determine the stability of the studies, and funnel plots were used to determine the potential publication bias.The effect sizes of the outcome indicators were expressed as odds ratio (OR) with 95% confidence intervals (CIs), and P < .05 was used to indicate statistical significance.

Results of Literature Screening
The initial screening of the literature involved 1199 articles.Using Endnote software and manual screening, duplicates were removed, leaving 717 articles.After reading the abstract and title, 482 articles remained.Further reading of the full article reveals 243 articles relevant to our study.][20][21][22][23][24][25][26][27][28] The detailed Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart of the study selection process was presented in Figure 1.

Basic characteristics of the included literature
This study included literature sources from 2 countries, spanning from 2014 to 2023.A total of 1299 hemodialysis patients who used autologous arteriovenous fistulae were examined.The study design consisted of randomized controlled trials, and the interventions tested were rope ladder cannulation, multiple single cannulation, and buttonhole cannulation.The experimental group comprised 646 cases, while the control group had 595 cases.The quality of the included literature was assessed using Figures 2 and 3.The characteristics of the included studies was presented in Table 1.

Effect of multiple single cannulation technique on the incidence of angiomas in arteriovenous fistulae.
The effect of multiple single cannulation technique on the incidence of angiomas in arteriovenous fistulae was evaluated in twelve papers involving hemodialysis patients.The results, which showed no heterogeneity among the included literature (I 2 = 0%, P = .92),indicated that the multiple-single cannulation technique was effective in reducing the incidence of aneurysms when compared to rope ladder cannulation and buttonhole cannulation (OR = 0.19, 95% CI = 0.10-0.35,P < .05).This difference was statistically significant (Fig. 4).The combined results of the literature were subjected to a funnel plot test, which revealed no significant asymmetry in the scatter points,indicating minimal publication bias as shown in Figure 5.

Effect of multiple single cannulation techniques on the incidence of arteriovenous fistulae stenosis.
23]27,28] The results showed (I 2 = 0%, P = .96),there was no heterogeneity in the included literature, and using a fixed-effects model, multiple single cannulation was able to reduce the incidence of AVF stenosis compared with rope ladder cannulation and buttonhole cannulation (OR = 0.22, 95% CI = 0.13-0.39,P < .05],and the difference was statistically significant, as shown in Figure 6.

Effect of multiple single cannulation techniques on
the incidence of thrombosis in arteriovenous fistulae.6 publications assessing the impact of multiple single cannulation technique on the incidence of thrombosis in arteriovenous fistulae. [11,19,20,22,23,25]he results showed (I 2 = 0%, P = .88),therewas no heterogeneity in the included literature, and using a fixed-effects model, multiple single cannulation techniques reduced the incidence of arteriovenous fistula thrombosis compared with rope ladder cannulation and buttonhole cannulation [OR = 0.17, 95% CI = 0.07-0.39,P < .05],and the difference was statistically significant, as shown in Figure 7.

Effect of multiple single cannulation techniques on the incidence of arteriovenous fistula.
Seven publications assessed the effect of multiple single cannulation techniques on the incidence of AVF occlusion in patients with arteriovenous fistulae., [16,19,21,23,24,26,28] the results showed (I 2 = 0%, P = .48),therewas no heterogeneity in the included literature, and using a fixedeffects model, multiple single cannulation reduced the incidence of arteriovenous fistula occlusion compared with rope ladder cannulation and buttonhole cannulation [OR = 0.28, 95% CI = 0.14-0.55,P < .05],and the difference was statistically significant, as shown in Figure 8.

The effect of multiple single cannulation techniques on the incidence of blood leakage from arteriovenous fistulae.
][26][27][28] The results showed (I 2 = 18%, P = .29),therewas mild heterogeneity in the included literature, and using a fixed-effects model, multiple single cannulation was able to reduce the incidence of blood oozing from the arteriovenous fistula compared to rope ladder cannulation and buttonhole cannulation (OR = 0.13, 95% CI = 0.08-0.21,P < .05), the difference was statistically significant, as shown in Figure 9.

Effect of multiple single cannulation techniques on the success rate of a single cannulation of arteriovenous fistula.
[26] The results showed (I 2 = 94%, P < .1)there was heterogeneity in the included literature and analyzed using a random-effects model, multiple single cannulations were able to improve the success rate of primary cannulation of arteriovenous fistula compared with cord cannulation and buttonhole cannulation (OR = 4.20; 95% CI = 1.78-9.95,P < .05),and the difference was statistically significant, as shown in Figure 10.

Effect of multiple single cannulation techniques on the incidence of arteriovenous fistula angiomas
When arteriovenous fistula blood vessels developed aneurysmal dilatation, it resulted in thinning of the skin epidermis.Continuous cannulation could easily lead to rupture and hemorrhage of the angiomas, posing a life-threatening risk to the patient.The occurrence of arteriovenous fistula angiomas varied from 5% to 60% in foreign countries, while a cross-sectional study involving 2547 patients in Hainan Province revealed a prevalence of 41.22% for AVF angiomas. [29]The primary reasons for the development of arteriovenous fistula angiomas in patients were as follows: (1) repeated cannulation causing damage to smooth muscle cells during dialysis, leading to intimal hyperplasia; (2) narrowing of the fistula, resulting in increased pressure in the anterior segment and consequent dilation of the blood vessel  lumen; (3) end-stage renal disease inflammatory factors, toxins, and other damage to the blood vessels; (4) increased venous blood flow speed due to surgery, leading to heightened internal vascular shear forces; and (5) genetic factors.The study demonstrated that the incidence of intra-arterial fistula hemangiomas was 1.73 times higher with area puncture compared to rope ladder cannulation, and 4.27 times higher compared to buttonhole cannulation. [29]Meta-analysis of this study showed that multiple single cannulation technique were able to reduce the incidence of intra-arterial fistula hemangiomas compared to rope ladder and buttonhole cannulation, which might be attributed to the fact that multiple single cannulation techniques had fewer cannulation sites, which resulted in less injury to the smooth muscle as well as reducing the risk of hemangiomas formed by intraventricular blood impingement on the cannulation site. [30]A meta-analysis showed that buttonhole cannulation was effective   in reducing the incidence of However, buttonhole cannulation was difficult to perform in clinical practice, making it more difficult to form and increasing the rate of infection in patients. [32]However, multisingle cannulation techniques did not require the formation of subcutaneous tunnels, the operation was simple, and could be carried out better in clinical practice, but also not because of the lack of subcutaneous tunnels, thus reducing the chances of arteriovenous fistula infection.

Effect of multiple single cannulation techniques on the incidence of stenosis and thrombosis in arteriovenous fistulae
Recent studies had shown that mature arteriovenous fistulae will gradually lose function with the increase of dialysis time, and the patency rate at 2 years was 75%, and stenosis was one of the main reasons for the loss of function of arteriovenous fistulae. [33]The mechanism of arteriovenous fistula stenosis was: (1) in the process of arteriovenous fistula maturation, the vessel wall of the vein will be thickened, the lumen will be dilated; (2) dialysis constant cannulation leads to venous blood vessel wall endothelial thickening, the formation of nonthrombotic stenosis; (3) inflammatory factors in the body, the toxin constant stimulation of the blood vessel wall formation of stenosis; (4) thrombus leads to arteriovenous fistula vessel stenosis. [34]The most common caused of thrombosis of the arteriovenous fistula was the stenosis of the arteriovenous fistula due to the thickening of the intima-media wall of the venous vessels. [35]Tordoir's study showed that 85% of arteriovenous fistula thrombosis was caused by arteriovenous fistula stenosis. [36]Therefore, the occurrence of stenosis and thrombosis   in arteriovenous fistulas were mutually reinforcing.In our study, we showed that multiple single cannulation techniques was more effective in reducing the incidence of arteriovenous fistula stenosis and thrombosis than rope ladder cannulation and buttonhole cannulation.Meta-analysis by Wang Liping et al [37] showed that buttonhole cannulation was more effective in reducing the incidence of arteriovenous fistula stenosis than rope ladder cannulation, which indirectly supports our study.Indirectly, this supported our findings.The reason for this might be that multiple single cannulation techniques was less damaging to the arteriovenous fistula vessels due to fewer cannulation points, and at the same time, changing the cannulation points reduces the possibility of endothelial hyperplasia in the arteriovenous fistula vessel wall.Some studies had shown that there would be granulation tissue around the tunnel of the button, and there would be skin hyperplasia in the vicinity of the granulation tissue, but the hyperplasia will subside after 3 months of changing the cannulation points. [38]Multiple single cannulation technique sited with fewer cannulation sites and different cannulation sites for each dialysis session reduced the chance of vascular tissue hyperplasia in the arteriovenous fistula, thus reducing the likelihood of thrombosis and stenosis in the arteriovenous fistula.

Effect of multiple single cannulation techniques on the incidence of blood leakage from arteriovenous fistulae
There was a lack of definition and quantification of blood leakage from an arteriovenous fistula. [39]The occurrence of blood leakage was related to the size of the needle used during cannulation, the nurse's cannulation technique, and the use of anticoagulants and subcutaneous fat. [40]In our study, we showed that multiple single cannulations were more effective than rope ladder cannulation and buttonhole cannulations in reducing blood seepage from arteriovenous fistulas, probably because multiple single cannulation techniques with repeated cannulation at fixed cannulation points resulted in endothelial hyperplasia in the patient's arteriovenous fistula, which altered the physiologic conditions of the vessels and changed their brittleness, thus decreasing the incidence of blood seepage.

Effect of multiple single cannulation technique on the success rate of a single cannulation
The vascular condition of the patient was closely related to the patient's underlying disease. [35]However, the cannulation success rate was related to the nurse's cannulation technique as well as the patient's vascular condition. [40]Fistula surgery results in a change in the anatomy of the patient's veins, making it more difficult for nurses to cannulation the vessels.The current study suggested that buttonhole cannulation improves the success rate of single cannulation of arteriovenous fistula. [41]The results of our study showed that multiple single cannulation technique had a higher success rate of single cannulation than rope ladder cannulation and buttonhole cannulation, and the results of meta-analysis by Yang et al [30] also showed that buttonhole blunt-needle cannulation was able to increase the success rate of 1 cannulation in arteriovenous fistula compared with rope ladder cannulation, which was similar to our results.The reason for this might be that multiple single cannulation techniques caused endothelial hyperplasia of the venous wall of the arteriovenous fistula, resulting in a thickening of the vessel wall, which changed the brittleness of the vessel, thus increasing the success rate of the cannulation.

Conclusion
Through a meta-analysis of 13 randomized controlled studies, this study concluded that multiple single cannulation technique can effectively reduce the incidence of angiomas, thrombosis, blood leakage, and stenosis in arteriovenous fistulae.Additionally, these techniques increase the success rate of nurses' single cannulation, reduce complications associated with arteriovenous fistulae, and prolong the use of arteriovenous fistulae.Ultimately, this leads to an extended life cycle for hemodialysis patients.

Limitations
The researcher is uncertain if some of the included literature in the study was blinded to patients, which could have affected the results.There is a lack of similar literature from foreign studies, which has the potential to influence the population use of multiple single cannulation technique.The definition of multiple single cannulation technique varies both nationally and internationally, so there may be relevant literature not yet included in the study that could impact the results.

Figure 1 .
Figure 1.PRISMA flow diagram detailing the study selection process.PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Table 1
Basic characteristics of the included literature Year b,d,e Note: a: stenosis, b: hemangioma c: success rate of 1 cannulation, d: thrombus,e: insufficient distal perfusion,f: occlusion of fistula,g: blood leakage, N: denotes failure to extract data in the literature.AVF = arteriovenous fistula.

Figure 4 .
Figure 4. Forest plot of the effect of multiple single cannulations technique on the incidence of angiomas.

Figure 5 .
Figure 5. Funnel plot of the effect of multiple single cannulation technique on the incidence of hemangiomas.

Figure 6 .
Figure 6.Forest plot of the effect of multiple single cannulation technique on stenosis.

Figure 7 .
Figure 7. Forest plot of the effect of multiple single cannulation technique on the incidence of thrombosis.

Figure 8 .
Figure 8. Forest plot of the effect of multiple single cannulation technique on the incidence of internal fistula occlusion.

Figure 9 .
Figure 9. Forest plot of the effect of multiple single cannulation technique on the incidence of blood seepage.

Figure 10 .
Figure 10.Forest plot of the effect of multiple single cannulation on the success rate of a single cannulation.